Principles which govern surface recognition, intra- and intermolecular assembly and function of peptides and proteins are being studied. Molecular recognition by peptides and proteins underlies essentially all biological functions of these substances, emphasizing the importance of understanding surface organization and dynamics in determining molecular order and function. This issue has been addressed with the neurohypophysial hormones oxytocin and vasopressin and associated neurophysins, which form cooperative peptide-protein complexes that act as storage forms for the polypeptides in neurosecretory granules, and the hormone-neurophysin precursors which also appear to self-associate into forms likely to exist in granules before processing. The nature and structural interrelationships between the self-association and hormone binding surfaces in neurophysins that give rise to cooperative complexes have been studied, using natural hormones and hormone mutants obtained by chemical synthesis. In addition, sequence-variant mutants of precursor have been prepared by semisynthesis and their interaction properties are being studied. Separately, underlying principles which determine surface recognition and consequent molecular order are being evaluated by studying the effect of synthetic sequence mutation on the peptide-protein assembly of semisynthetic ribonuclease-S, using high resolution structure of a modeled semisynthetic ribonuclease-S as a starting point. The data are being used to examine rules of protein self-assembly and to establish general guidelines for protein engineering. In addition, protein engineering by recombinant DNA methods is being used to examine the general usefulness of site-specific random sequence mutation, with initial experiments being carried out using lambda repressor. Eventually, correlation of helical packing, domain assembly, flexibility and proteolysis should be useful to better understand the regulation of enzymatic processing of endocrine "multi-domain" precursors.